Suppression of cryptococcosis and histoplasmosis by ketoconazole in athymic nude mice

Abstract

Congenitally athymic nude (nu/nu) mice are more susceptible to disseminated cryptococcosis and histoplasmosis than their heterozygous (nu/ + ) thymus-bearing litter-mates. The therapeutic efficacy of ketoconazole, an orally absorbable antifungal agent, was evaluated in nu/nu and nu/ + mice infected intraperitoneally with Cryptococcus neoformans and Histoplasma capsulatum. Two- to five-week courses of ketoconazole significantly prolonged the survival of nu/nu mice infected with either fungus in dose-dependent fashion, but death eventually followed discontinuance of therapy. More significant protection was seen in nu/ + mice infected with C. neoformans, and markedly lower fungal counts in organs, with some negative cultures, were seen in ketoconazole-treated nu/ + mice infected with H. capsulatum. These studies indicate that ketoconazole is effective against both fungi, although results of treatment are much better in the immunologically intact nu/ + host.